Many complex tissues in the adult mammal fail to regenerate following injury or disease. For example, a critical sized defect in bone will fail to regenerate. Ligaments do not regenerate if destroyed by disease or injury such as the dental ligament in periodontal disease. Dermal ulcers in the elderly, diabetic, or individuals with venous stasis pathology can become chronic wounds that fail to heal. One approach to repair damage of this sort is referred to as Tissue Engineering wherein cells on matrices are used to affect tissue repair that would not occur without such an intervention. Tissue scaffolds are known in the art, see for example U.S. Pat. Nos. 6,451,060, 5,830,708, 6,284,284, 6,143,293, 6,306,169, 6,319,712, 6,228,117, and 5,916,585, and PCT and U.S. Patent Applications WO 99/03979, WO 01/03750, WO 01/85226, and US2003/0023316.
U.S. Pat. No. 4,963,489 discloses a living stromal tissue prepared in vitro, having stromal cells and connective tissue proteins naturally secreted by the stromal cells attached to and substantially enveloping a framework composed of a biocompatible, non-living material formed into a three dimensional structure having interstitial spaces bridged by the stromal cells.
U.S. Pat. No. 5,830,708 discloses the production of an extracellular matrix secreted by stromal cells onto a three dimensional substrate. The substrate is composed of a biocompatible, non-living material formed into a three-dimensional structure having interstitial spaces bridged by the stromal cells. The cells are removed to provide a cell free implant.
U.S. Pat. No. 6,140,039 discloses a three-dimensional filamentous tissue providing the function of a tendon or a ligament which has fibroblasts and collagen naturally secreted by the fibroblasts attached to and substantially enveloping a three-dimensional filamentous framework composed of a biocompatible, non-living material having interstitial spaces bridged by the fibroblasts.
However, such structures have limitations. The method of cell seeding is usually inefficient, as the cells must attach to the fibers, and the pores allow many of the cells to pass through the scaffold, resulting in inefficient cell seeding. The cells must fill the interstitial spaces by proliferation of the cells attached to the scaffold at the edge of the interstitial space, and must then deposit an extracellular matrix. This is a relatively slow process, and results in loss of synthesized and secreted matrix into the media, until the cells provide a confluent layer of cells across the interstitial space. This can result in an inconsistent manufacturing process. There is therefore a need to increase efficiency of the cell attachment and growth process, and deposition of the extracellular matrix.
Therefore, it would be advantageous to provide an improved scaffold system that results in increased efficiency of cell attachment, allowing cells to attach across large areas of the scaffold, rather than only at the edge of interstitial spaces. A scaffold that provides for larger number of cells to attach would result in more rapid formation of a confluent layer and more rapid matrix deposition compared to scaffolds wherein cells attach only to fibers and must grow to fill interstitial spaces.